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排序方式: 共有8227条查询结果,搜索用时 15 毫秒
1.
《Arabian Journal of Chemistry》2022,15(1):103492
Matrix metalloproteinases (MMPs) are a large family of zinc-dependent endoproteases known to exert multiple regulatory roles in tumor progression. A variety of chemical classes have been explored for targeting individual MMP isoforms. In the present study, we further developed our isatin based scaffold BB0223107 capable of binding to and inactivating MMP-2 in a zinc-independent manner (Agamennone et al., 2016). Forty four new compounds were synthesized based on the modified BB0223107. All compounds were tested in enzyme inhibition assays against MMP-2, ?8 and ?13. SAR studies demonstrated that 5-het(aryl)-3-aminoindolin-2-ones (37–39) were active toward MMP-2 and MMP-13. The most potent compounds 33 and 37 displayed an IC50 of 3 µM against MMP-13 and showed a negligible activity toward MMP-8; almost all new compounds were inactive toward MMP-8. Replacement of the isatin ring with a biaryl system (compound 33) did not decrease the potency against MMP-13 but reduced the selectivity. Structure-based computational studies were carried out to rationalize the inhibitory activity data. The analysis of binding geometries confirmed that all fragments occupied the S1′ site in the three enzymes while no ligand was able to bind the catalytic zinc ion. To the best of our knowledge, this is the first example of 3-aminoindolin-2-one-based MMP inhibitors that, based on the computer modeling study, do not coordinate the zinc ion. Thus, the het(aryl)-3-aminoindolin-2-one derivatives emerge as a drug-like and promising chemotype that, along with the hetaryl variations, represents an alternative and thrifty tool for chemical space exploration aimed at MMP inhibitor design. 相似文献
2.
Rongzhen Wu Hongyu Chen Dr. Ninghui Chang Yuzhi Xu Prof. Dr. Jiao Jiao Prof. Dr. Hailong Zhang 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(6):1166-1195
Bryostatins are a class of naturally occurring macrocyclic lactones with a unique fast developing portfolio of clinical applications, including treatment of AIDS, Alzheimer's disease, and cancer. This comprehensive account summarizes the recent progress (2014–present) in the development of bryostatins, including their total synthesis and biomedical applications. An emphasis is placed on the discussion of bryostatin 1 , the most-studied analogue to date. This review highlights the synthetic and biological challenges of bryostatins and provides an outlook on their future development. 相似文献
3.
Capillary Electrophoresis Chiral Separation for Enantiomeric Purity Determination of a Basic Drug in Pharmaceutical Formulations 总被引:1,自引:0,他引:1
Capillary electrophoresis using a running buffer composed of β-cyclodextrin as the chiral selector and ethanolamine mesylate at pH 9.6 is being used to monitor the stereochemical stability of a hydrophobic drug, containing two chiral centers, in two different formulated self-emulsifying drug delivery system (SEDDS) products. The separation takes place in less than 25 min. Strategies for enhancing the method reproducibility and detection sensitivity in the lower potency formulation are presented. The results demonstrating the specificity, assay precision, recovery, linearity and range achieved during the method validation experiments are presented in this paper.Presented at: CE in the Biotechnology and Pharmaceutical Industries: 7th Symposium on the Practical Applications for the Analysis of Proteins, Nucleotides and Small Molecules, Montreal, Canada, August 12–16, 2005. 相似文献
4.
5.
Dmitry S. Zimnitsky Tatiana L. Yurkshtovich Pavel M. Bychkovsky 《Journal of polymer science. Part A, Polymer chemistry》2004,42(19):4785-4791
Samples of oxidized cellulose (OC) with various carboxyl contents and degrees of crystallinity were obtained by the oxidation of native and mercerized cellulose with a solution of nitrogen(IV) oxide in CCl4. A detailed characterization of these OC samples was performed. The effect of oxidation conditions (concentration of N2O4 in the solution and oxidation time) and starting cellulose material on OC characteristics (carboxyl, carbonyl and nitrogen content, degree of crystallinity and polymerization, surface area and swelling, and acidic properties) was investigated. Reactivity in the oxidation process was higher in mercerized cellulose than in native cellulose. The action of dilute solutions (10–15%) of N2O4 did not affect the degree of crystallinity of cellulose samples. Under these conditions, the oxidation took place mainly in amorphous regions and on the surface of crystallites. Oxidation in a concentrated (40%) N2O4 solution led to the destruction of crystallites, which increased the surface area and swelling of cellulose in water. The surface area and the swelling of OC samples increased with a decrease in the index of crystallinity. The acidic properties of OC were shown to increase with an increase of swelling in water. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4785–4791, 2004 相似文献
6.
文[1]曾报道将蓖麻油提取物精制品制成乳剂和多相脂质体,进行动物体内外抗癌活性实验,结果表明该提取物具有较强的抗癌活性,但其抗癌活性成分的组成和含量尚不清楚.本实验就蓖麻油提取物的组成和含量进行气相色谱分析. 相似文献
7.
8.
A nanoscale
multivalent platinum drug based on a poly(amidoamine) [PAMAM] dendrimer (generation
4.5, carboxylate surface) has been synthesized and fully characterized using
a variety of spectroscopic, chromatographic and thermal methods. Treatment
of the dendrimer with an aqueous solution containing an excess diaquo(cis-1,2-diaminocyclohexane)platinum(II) produces
a conjugate containing approximately forty (diaminocyclohexane)platinum(II)
moieties at the surface of the dendrimer. This material undergoes smooth two-stage
thermal decomposition to provide residual platinum oxide reflecting the platinum
loading in the drug. 相似文献
9.
复方单硝酸异山梨酯-阿司匹林双缓释微丸胶囊的研制(Ⅱ) 总被引:2,自引:0,他引:2
以乙基纤维素、丙烯酸树脂Ⅱ和丙烯酸树脂Ⅲ为骨架材料分别制备单硝酸异山梨酯和阿司匹林混合骨架缓释微丸,并通过包薄膜衣进一步控制药物的释放。通过测定微丸的释放度对处方工艺进行评价,选择最佳微丸灌装胶囊.胶囊中两种药物均达到良好的缓释效果。符合中国药典对缓释制剂的要求.其体外释放过程同时符合Higuchi方程和一级释药方程,R^2值均在0.995以上。 相似文献
10.
工件带到达时间的两阶段柔性流水作业的近似算法 总被引:1,自引:0,他引:1
研究了工件带到时间的两阶段柔性流水作业的排序问题,基于求解流水作业和平行机问题的算法思想,提出两个相应的近似算法H(R)和H(MR(?)),证明了这两个算法的最坏情况性能比分别为3-1/m和2/5-1/m,讨论了界的紧性,并利用数值模拟以分析算法与最优值的近似性能比. 相似文献